Nucleophilic Substitution Reactions of 2‐Methoxy‐3‐X‐5‐nitrothiophenes: Effect of Substituents and Structure–Reactivity Correlations

Abstract

A kinetic study is reported for reactions of 2‐methoxy‐3‐X‐5‐nitrothiophenes 1a–d (X = SO2CH3, CO2CH3, CONH2, H) with piperidine in different solvents at 20°C. It is shown that the reactions take place through a SNAr mechanism with the initial nucleophilic addition step being rate limiting. The satisfactory Hammett correlations (log k1 vs. σnormalp−) obtained in the present system confirms that a 3‐X substituent exerts an effect on the 2‐position of the same type as that exerted from the 5‐position. The second‐order rate constants associated with these reactions are employed to determine the electrophilicity parameters E of the thiophenes 1a–d according to the relationship log k (20°C) = s(E + N) (Angew. Chem., Int. Ed. Engl. 1994, 33, 938–957). The E values of 1a–d are found to cover a range from −21.33 to −17.18, going from 1d, the least reactive, to 1a, the most reactive thiophene. Interestingly, a linear correlation (r2 = 0.9910) between the electrophilicity parameters E determined in this work and the Hammett's σnormalp− constants values has been observed and discussed. On the other hand, we have found that the reported rate constants of some thiophenes 1 complexation by the methoxide ion in methanol are 3.5–73.5 times higher than predicted by Mayr's approach.

The ambident electrophilic behavior of 5‐nitro‐3‐X‐thiophenes in σ‐complexation processes

“…On the other hand, the high positive sensitivity constant ρ X values (6.64–6.99) estimated in the present study for the charge transfer from the phenoxide anion to thiophene are higher than that (4.02) reported by Spinelli and co‐workers for reactions of various 2‐( p ‐nitrophenoxy)‐3‐X‐5‐nitrothiophenes 12 (X = SO 2 CH 3 , CO 2 CH 3 , CONH 2 , H, CN, NO 2 , Br, CH 3 ) with piperidine performed in methanol at 20°C [Ref. ] than the values of 2.06 (in DMSO), 2.22 (in CH 3 CN), and 2.46 (in 91% CH 3 OH‐9% CH 3 CN) obtained by Echaieb and co‐workers for the reactions of 2‐methoxy‐3‐X‐5‐nitrothiophenes 13 (X = SO 2 CH 3 , CO 2 CH 3 , CONH 2 , H) with piperidine at 20°C . The existence of such large ρ X values indicates that the steric effects of substituents ortho to the site of nucleophilic attack are minimized and confirms that a 3‐X substituent in thiophene exerts an effect on the 2‐position of the same type as that exerted from the 5‐position .…”

“…Figure summarizes the electrophilicity parameters E , which have been obtained in the present study for both thiophenes, and these data have been compared with those recently reported by Guo and Mayr for o ‐chloranil 14 and 2,5‐dichloroquinone 15 , together with 2‐methoxy‐3,5‐dinitrothiophene 16 , 2‐methoxy‐3cyano‐5‐nitrothiophene 17 , 1,3,5‐trinitrobenzene 18 , 2,4,6‐trinitroanisole 19 , and 2,4,6‐tris(trifluoromethanesulfonyl) anisole 20, previously investigated by our laboratory.…”

“…] than the values of 2.06 (in DMSO), 2.22 (in CH 3 CN), and 2.46 (in 91% CH 3 OH‐9% CH 3 CN) obtained by Echaieb and co‐workers for the reactions of 2‐methoxy‐3‐X‐5‐nitrothiophenes 13 (X = SO 2 CH 3 , CO 2 CH 3 , CONH 2 , H) with piperidine at 20°C . The existence of such large ρ X values indicates that the steric effects of substituents ortho to the site of nucleophilic attack are minimized and confirms that a 3‐X substituent in thiophene exerts an effect on the 2‐position of the same type as that exerted from the 5‐position . These results confirm the role of the hyper‐ortho relationship in the thiophene compounds.…”

Reactions of N1-Methyl-4-nitro-2,1,3-benzoselenadiazolium Tetrafluoroborate with Aliphatic and Cyclic Amines in Acetonitrile: Kinetic and Structure-Reactivity Correlations

“…predicts second‐order rate constants for the additions of propylamine and morpholine to 5‐(4‐ N , N ‐dimethylaminobenzylidene)‐1,3‐dimethyl‐2,4,6‐(1H,3H,5H)pyrimidinetrione with 28 and 31 times faster than measured . Recently, Echaieb and co‐workers have found that the reported rate constants of some thiophenes complexation by the methoxide ion in methanol are 3.5–73.5 times higher than predicted by Mayr's approach .…”

“…for the reactions of the benzoselenadiazolium cation 1 with the amines 2d–f deviate by less than a factor 56 from those measured. The relatively large reactivity ratios values obtained are acceptable, because, usually predicts rate constants of polar nucleophilic addition and substitution reactions with an accuracy of factor 10–100 . Seeliger and co‐workers have demonstrated that Eq.…”